Context: Endogenous glucocorticoid excess (Cushing's syndrome) predominantly increases postprandial glucose concentration. The pattern of hyperglycemia induced by prednisolone has not been well characterized. Objective: Our objective was to define the circadian effect of prednisolone on glucose concentration to optimize management of prednisolone-induced hyperglycemia. Design and Setting: This was a cross-sectional study in a teaching hospital. Participants: Participants included 60 consecutive consenting subjects with chronic obstructive pulmonary disease admitted to hospital: 13 without known diabetes admitted for other indications and not treated with glucocorticoids (group 1), 40 without known diabetes admitted with an exacerbation of chronic obstructive pulmonary disease and treated with prednisolone (group 2, prednisolone = 30 ± 6 mg/d), and seven with known diabetes treated with prednisolone (group 3, prednisolone = 26 ± 9 mg/d). Main Outcome Measure: Interstitial glucose concentration was assessed during continuous glucose monitoring. Results: Significantly more subjects in group 2 [21 of 40 (53%), P = 0.02] and group 3 [seven of seven (100%), P = 0.003] recorded a glucose of at least 200 mg/dl (≥11.1 mmol/liter) during continuous glucose monitoring than in group 1 [one of 13 (8%)]. The mean glucose concentration between 2400-1200 h for group 3 (142 ± 36 mg/dl) was significantly greater than in the other two groups (P < 0.005), whereas mean glucose concentrations between 2400-1200 h in group 1 (108 ± 16 mg/dl) and group 2 (112 ± 22 mg/dl) were not significantly different. In contrast, the mean glucose concentrations between 1200-2400 h for group 2 (142 ± 25 mg/dl) and group 3 (189 ± 32 mg/dl) were both significantly greater than group 1 (117 ± 14 mg/dl, P < 0.05 for both comparisons). Conclusions: Prednisolone predominantly causes hyperglycemia in the afternoon and evening. Treatment of prednisolone-induced hyperglycemia should be targeted at this time period.